A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.
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DOI：
10.1371/journal.pone.0092732
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kitamura D
中科院分区：
文献类型：
--
作者：
Moutai T;Yamana H;Nojima T;Kitamura D
免疫疗法，如过继转移T细胞或自然杀伤细胞，或单抗(Moab)治疗，最近已被认为是治疗癌症患者的有效手段。然而，过继转移产生肿瘤特异性抗体的B细胞或浆细胞尚未被应用于治疗，因为长期培养和选择性扩增抗原特异性B细胞在技术上一直非常困难。在这里，我们描述了一种使用B细胞过继转移的新型癌症免疫疗法。我们证明了由小鼠幼稚B细胞在体外诱导的生发中心样B细胞(IGB细胞)成为浆细胞，并在未受照射的受者小鼠的骨髓中产生抗体一个多月。当转移到小鼠体内时，产生针对替代肿瘤抗原的抗体的IGB细胞抑制了表达相同抗原的小鼠黑色素瘤细胞的肺转移和生长，并延长了受体的生存时间。此外，我们开发了一种称为FAIS的新型培养系统，利用IGB细胞对Fas诱导的细胞死亡敏感的事实，选择性地扩增抗原特异性IGB细胞，除非它们的抗原受体被膜结合的抗原连接起来。在过继免疫治疗模型中，所选择的IGB细胞有效地抑制了黑色素瘤细胞的肺转移。由于人类血液B细胞可以在类似于小鼠IGB细胞培养的培养条件下作为IGB细胞进行繁殖，我们的数据表明，通过在体外选择癌症抗原特异性IGB细胞过继转移来治疗癌症患者是可能的。这种新的过继免疫疗法应该是摩押药物艰难开发的替代方案，这些药物目前还没有有效的治疗方法。
Immunotherapies such as adoptive transfer of T cells or natural killer cells, or monoclonal antibody (MoAb) treatment have recently been recognized as effective means to treat cancer patients. However, adoptive transfer of B cells or plasma cells producing tumor-specific antibodies has not been applied as a therapy because long-term culture and selective expansion of antigen-specific B cells has been technically very difficult. Here, we describe a novel cancer immunotherapy that uses B-cell adoptive transfer. We demonstrate that germinal-center-like B cells (iGB cells) induced in vitro from mouse naïve B cells become plasma cells and produce IgG antibodies for more than a month in the bone marrow of non-irradiated recipient mice. When transferred into mice, iGB cells producing antibody against a surrogate tumor antigen suppressed lung metastasis and growth of mouse melanoma cells expressing the same antigen and prolonged survival of the recipients. In addition, we have developed a novel culture system called FAIS to selectively expand antigen-specific iGB cells utilizing the fact that iGB cells are sensitive to Fas-induced cell death unless their antigen receptors are ligated by membrane-bound antigens. The selected iGB cells efficiently suppressed lung metastasis of melanoma cells in the adoptive immunotherapy model. As human blood B cells can be propagated as iGB cells using culture conditions similar to the mouse iGB cell cultures, our data suggest that it will be possible to treat cancer-bearing patients by the adoptive transfer of cancer-antigen-specific iGB cells selected in vitro. This new adoptive immunotherapy should be an alternative to the laborious development of MoAb drugs against cancers for which no effective treatments currently exist.
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DOI：
10.1038/nrc3258
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1038/nri3191
发表时间：
2012-03-22
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Restifo NP;Dudley ME;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
影响因子：
4.7
作者：
Lee, Sylvia;Margolin, Kim
通讯作者：
Margolin, Kim
影响因子：
46.9
作者：
Love, J. Christopher;Ronan, Jehnna L.;Ploegh, Hidde L.
通讯作者：
Ploegh, Hidde L.